Kisspeptin, a 54-amino acid peptide (KP-54), has recently been found to act as a regulator of the gonadotropic axis (Seminara et al., 2003) in addition to having roles as a metastasis suppressor and in trophoblast invasion. KP-54 and the C terminal fragments KP-13 and KP-10 bind to the recently de-orphanised KISS1 receptor, previously known as GPR54. Kisspeptin inhibits matrix metalloproteases-2 and -9, both of which are produced by cardiomyocytes. Additionally, we have reported vasoconstrictor activity of the kisspeptins in human umbilical vein and atherosclerosis-prone vessels (Mead et al., 2007) and have detected kisspeptin and KISS1 immunoreactivity in endocardial endothelial cells and cardiomyocytes of the human heart (Mead, unpublished data). We hypothesise that kisspeptin is an inotropic agent in both human and mouse heart, acting through the KISS1 receptor. <p>4mm human atrial appendage strips and atria from male 129S6/SvEv mice (20-30g; euthanised by CO₂ inhalation) were set up in organ baths and paced using field stimulation (<4V). Tension on the tissue was adjusted to 50% of optimum resting tension before construction of cumulative concentration response curves to KP-54, -13 and -10 and termination by CaCl₂ addition (6.7 mM). Agonist responses were expressed as %CaCl₂ and data are mean ± s.e.mean. <p>In human paced atrial appendage, KP-10, KP-13 and KP-54 induced positive inotropic effects with comparable potency (pD₂: 10.60±0.73, 10.38±0.57, 10.10±0.44) and maximal response (E_max: 75.7±8.0, 85.2±14.0, 89.8±13.9) respectively (n=5; P>0.05, ANOVA). In mouse atria, KP-54 also induced positive inotropic effects (pD₂: 10.19±0.51, E_max: 27.3±5.8; n=4). <p>In conclusion, kisspeptins appear to act as inotropic agents in both the human and mouse heart. All three peptides had comparable potency, indicating that the activity is retained in the final 10 amino acids.